ICA-1: A novel antiproliferative and anticancer drug for neuroblastoma

Abstract

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Neuroblastomas are highly lethal tumors and 85% of cerebral neuroblastoma occurs in children and 15% in adults. Neuroblastoma is the fourth most common type of cancer in children. According to the American Cancer Society, there are approximately 650 new cases of neuroblastoma each year in the United States. Despite significant educational efforts, improved diagnostic techniques, and rigorous therapies, neuroblastoma control remains static. To address this health issue, the objectives of this research was to investigate the use protein kinase C-iota (PKC-ι) inhibitors on the proliferation of neuroblastoma cells. Previous work has shown that inhibition of PKC-ι is a promising means by which to prevent and treat certain cancers. Here, we report the identification of a PKC-ι inhibitor (1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy) methyl]cyclopentyl]-,[1R-(1α, 2β, 3β, 4α)] (ICA-1) that targets a unique sequence (amino acid residues 469-475) in the catalytic domain of PKC-ι, inhibits PKC-ι activity and is effective in blocking the proliferation of BE(2)C neuroblastoma cells. Our data support significant proof of concept that ICA-1 inhibits the proliferation of neuroblastoma cells and may be a novel chemotherapeutic for the treatment of patients with neuroblastoma.